Abstract：
Previous research reported that prolonged benzene exposure during in utero fetal development causes greater fetal abnormalities than in adult-stage exposure. This phenomenon increases the risk for disease development at the fetal stage, particularly carcinogenesis, which is mainly associated with hematological malignancies. Benzene has been reported to potentially act via multiple modes of action that target the hematopoietic stem cell (HSCs) niche, a complex microenvironment in which HSCs and multilineage hematopoietic stem and progenitor cells (HSPCs) reside. Oxidative stress, chromosomal aberration and epigenetic modification are among the known mechanisms mediating benzene-induced genetic and epigenetic modification in fetal stem cells leading to in utero carcinogenesis. Hence, it is crucial to monitor exposure to carcinogenic benzene via environmental, occupational or lifestyle factors among pregnant women. Benzene is a well-known cause of adult leukemia. However, proof of benzene involvement with childhood leukemia remains scarce despite previously reported research linking incidences of hematological disorders and maternal benzene exposure. Furthermore, accumulating evidence has shown that maternal benzene exposure is able to alter the developmental and functional properties of HSPCs, leading to hematological disorders in fetus and children. Since HSPCs are parental blood cells that regulate hematopoiesis during the fetal and adult stages, benzene exposure that targets HSPCs may induce damage to the population and trigger the development of hematological diseases. Therefore, the mechanism of in utero carcinogenicity by benzene in targeting fetal HSPCs is the primary focus of this review.
摘要：
先前的研究报道，子宫内胎儿发育过程中长时间的苯暴露会导致比成人阶段暴露更大的胎儿异常。这种现象增加了胎儿期疾病发展的风险，特别是致癌作用，主要与血液恶性肿瘤有关。据报道，苯可能通过靶向造血干细胞（HSC）生态位的多种作用模式起作用。HSC和多谱系造血干细胞和祖细胞（HSPC）所在的复杂微环境。氧化应激,染色体畸变和表观遗传修饰是介导苯诱导的胎儿干细胞遗传和表观遗传修饰导致子宫内癌变的已知机制之一。因此，通过环境监测致癌苯的暴露是至关重要的，孕妇的职业或生活方式因素。苯是成人白血病的众所周知的原因。然而,尽管先前有研究将血液病的发生率与母体苯暴露联系起来，但儿童白血病与苯有关的证据仍然很少。此外，越来越多的证据表明，母体苯暴露能够改变HSPCs的发育和功能特性，导致胎儿和儿童血液系统疾病。由于HSPC是在胎儿和成人阶段调节造血的亲代血细胞，针对HSPCs的苯暴露可能会对人群造成损害并引发血液病的发展。因此,苯靶向胎儿HSPCs的子宫内致癌性机制是本综述的主要重点。
